Resilience, the ability to overcome stressful conditions, is found in most mammals and varies significantly among individuals. A lack of resilience can lead to the development of neuropsychiatric and sleep disorders, often within the same individual. Despite extensive research into the brain mechanisms causing maladaptive behavioral-responses to stress, it is not clear why some individuals exhibit resilience.  To examine if sleep has a determinative role in maladaptive behavioral-response to social stress, we investigated individual variations in resilience using a social-defeat model for male mice. Our results reveal a direct, causal relationship between sleep amount and resilience—demonstrating that sleep increases after social-defeat stress only occur in resilient mice. Further, we found that within the prefrontal cortex, a regulator of maladaptive responses to stress, pre-existing differences in sleep regulation predict resilience. Overall, these results demonstrate that increased NREM sleep, mediated cortically, is an active response to social-defeat stress that is both necessary and sufficient for promoting resilience. They also show that differences in resilience are strongly correlated with inter-individual variability in sleep regulation.

Male, C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME, USA; 000664) were seven-weeks old at the start of all studies. CD-1 retired male breeders (Charles Rivers, age 3 to 6 months upon arrival) were used as aggressors. All mice were singly housed on shaved, pine bedding upon arrival, maintained on a 12:12 L:D lighting cycle for the remainder of the study and randomly assigned to treatment groups. Food and water were available ad libitum. All procedures involving animals received prior approval from the Morehouse School of Medicine Institutional Animal Care and Use Committee (approved protocol 21-02).

Surgery: EEG and LFP electrodes.

Electroencephalography (EEG): EEG and Electromyography (EMG) electrodes were implanted in isoflurane (1.5–3%) anesthetized mice. Carprofen was given post operatively for two days. A prefabricated head mount (Pinnacle Technology Inc., Lawrence, KS) was used to position three stainless-steel epidural screw electrodes. The first electrode (frontal—located over the frontal cortex) was placed 1.5 mm anterior to bregma and 1.5 mm lateral to the central suture, whereas the second two electrodes (interparietal—located over the visual cortex and common reference) were placed 2.5 mm posterior to bregma and 1.5 mm on either side of the central suture. The resulting two leads (frontal–interparietal and interparietal–interparietal) were referenced contralaterally. A fourth screw served as a ground. Electrical continuity between the screw electrode and head mount was aided by silver epoxy. EMG activity was monitored using stainless-steel Teflon-coated wires that were inserted bilaterally into the nuchal muscle.  The head mount (integrated 2 × 3 pin socket array) was secured to the skull with dental acrylic. Mice were allowed to recover for at least 14 days before sleep recording.